This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. SPECIFIC AIMS 1: To compare the role of antigen specific IgA, IgG and IgM immune responses in macaques with different levels of immunity to SIV/SHIV infection. We will compare antigen specific IgA &IgG responses in macaques intravenously, intravaginally, and intrarectally inoculated with SIVmac251 (a highly pathogenic virus that consistently results in persistent viremia and AIDS) to macaques mucosally inoculated with low doses of SHIVsf162p3 (which usually results in low to undetectable plasma viremia and lack of disease progression). Antigen specific immunoglobulin responses will also be assessed in SIVmac251 inoculated macaques, which are able to control their infection and become long-term nonprogressors (LNTP). 2: To quantify effector memory B cells in macaques infected with SIV by different inoculation routes. Since the mucosal immune system is "compartmentalized" into mucosal and systemic arms, we hypothesize that mucosal immune responses may differ depending on the route of inoculation. Thus, effector memory B cells will be evaluated and quantified in different tissues including peripheral blood, intestines, lymph nodes, and BAL samples of intravenously and mucosally inoculated macaques. We will also quantify secretory IgA and IgG from both systemic and mucosal immune sites. Using this approach, we predict that we will be able to correlate SIV specific mucosal immune responses with reduction of viremia and protection from disease progression in macaques infected with pathogenic viruses.